Clinical Trials Register

Summary
EudraCT Number:	2016-003949-28
Sponsor's Protocol Code Number:	Inco_Ona1
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-08
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2016-003949-28

A.3

Full title of the trial

Incobotulinumtoxin versus Onabotulinumtoxin in the treatment of patients with overactive bladder syndrome

Incobotulinumtoxin A versus Onabotulinumtoxin A nel trattamento dei pazienti con sindrome da vescica iperattiva

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Efficacy and tolerability of incobotulinumtoxin A in comparison with onabotulinumtoxinA in patients with overactive bladder syndrome.

Efficacia e tollerabilit¿ della incobotulinumtoxin A in confronto alla onabotulinumtoxin A nella terapia di pazienti con vescica iperattiva.

A.3.2

Name or abbreviated title of the trial where available

Inco_Ona1

A.4.1

Sponsor's protocol code number

Inco_Ona1

A.5.4

Other Identifiers

Name:

Inco_Ona1

Number:

Inco_Ona1

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	PROF. ANTONELLA GIANNANTONI - CLINICA UROLOGICA - UNIVERSITà DI PERUGIA
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Clinica Urologica ad indirizzo Oncologico
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Universit¿ degli Studi di Perugia
B.5.2	Functional name of contact point	Clinica Urologica ad indirizzo Onco
B.5.3	Address:
B.5.3.1	Street Address	Via Dottori
B.5.3.2	Town/ city	Perugia
B.5.3.3	Post code	06132
B.5.3.4	Country	Italy
B.5.4	Telephone number	0755783898
B.5.5	Fax number	0755784416
B.5.6	E-mail	roberta.cagini@unipg.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	XEOMIN - 100 UNITA' DL50 POLVERE PER SOLUZIONE INIETTABILE 1 FLACONCINO DI VETRO
D.2.1.1.2	Name of the Marketing Authorisation holder	MERZ PHARMACEUTICALS GMBH
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	xeomin
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	93384-43-1
D.3.9.2	Current sponsor code	.
D.3.9.3	Other descriptive name	IncobotulinumtoxinA
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Tossina purificata dalle colture di C. botulinum
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	BOTOX - 100 UNIT¿ ALLERGAN POLVERE PER SOLUZIONE INIETTABILE 1 FLACONCINO
D.2.1.1.2	Name of the Marketing Authorisation holder	ALLERGAN PHARMACEUTICALS IRELAND
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	botox
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	93384-43-1
D.3.9.2	Current sponsor code	.
D.3.9.3	Other descriptive name	onabotulinumtoxin type A
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	tossina purificata dalle colture di C. botulinum

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

neurogenic overactive bladder

Vescica iperattiva neurogena

E.1.1.1

Medical condition in easily understood language

neurogenic overactive bladder

Vescica iperattiva neurogena

E.1.1.2

Therapeutic area

Diseases [C] - Symptoms and general pathology [C23]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10032081
E.1.2	Term	Other functional disorder of bladder
E.1.2	System Organ Class	100000004857

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The aim of the study is to compare Incobot/A versus Onabot/A in order to evaluate if the differencies in the pharmacologic formulations between the two drugs could affect their efficacy and safety in the treatment of neurogenic OAB. The study is aimed to assess the equivalence or the superiority of Incobotulinumtoxin A versus Onabotulinumtoxin A on the efficacy and safety parameters.

Studio di confronto tra Incobotulinumtossina A e Onabotulinumtossina A allo scopo di valutare se le differenze nelle caratteristiche farmacologiche tra le due neurotossine influenzino l¿efficacia e la tollerabilit¿ nella terapia della vescica iperattiva neurogena. Lo studio ¿ volto a dimostrare
l¿equivalenza o la superiorit¿ dell¿Incobotulinumtossina/A versus l¿Onabotulinumtossina/A a livello di efficacia clinica, e nella riduzione della comparsa di alcuni effetti collaterali.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria:

- patients (males and females) with neurogenic urge urinary incontinence (UUI) (with urgency, increase in day- time and night- time urinary frequency) and with urodynamic diagnosis of DO;
- 18- 80 years;
- women of childbearing age, who use a reliable method of contraception throughout the study period (a pregnancy test must be performed during enrolment in the study);
- spinal cord injury at or below T1, diagnosed at least 6 months before the screening in case of a vesico-sphincter dysfunction due to spinal cord injury;
- EDSS score = 6, in MS patients;
- patients refractory to anticholinergic therapy (= 1 anticholinergic agent)
- application of intermittent catheterizations to empty the bladder. In the case of spontaneous micturition, the patients should agree for the use of intermittent catheterizations, in case this will be necessary after treatment with the detrusor injection of botulinumtoxin A.

Urodynamic characteristics:

urodynamic diagnosis of DO, refractory to standard anticholinergics and naïve to intradetrusor injection of onabotulinumtoxin A.

The wash- out period after anticholinergics has to be of at least 3 weeks.

Criteri di inclusione: pazienti di entrambi i sessi, affetti da vescica iperattiva di varia eziologia (urgenza minzionale, incremento della frequenza urinaria diurna e notturna con incontinenza urinaria da urgenza) e con iperattività detrusoriale all’esame urodinamico. Età compresa tra 18 e 80 anni. Donne in età fertile che facciano uso di un metodo contraccettivo affidabile durante tutto il periodo dello studio (dovrà essere effettuato un test di gravidanza al momento dell’arruolamento allo studio). La disfunzione vescico- sfinterica secondaria a lesioni del midollo spinale dovrà essere localizzata a livello o al di sotto di T1. La lesione spinale dovrà essere in fase di stabilizzazione, con fuoriuscita certa dalla fase di shock spinale, e verificatasi almeno 6 mesi prima dello screening. Per quanto riguarda pazienti con Sclerosi Multipla verranno inclusi coloro con uno score alla EDSS inferiore o uguale a 6. Tutti i pazienti dovranno essere refrattari alla comune terapia con anticolinergici (= 1 anticolinergico). Verranno inclusi pazienti che svuotino la vescica mediante impiego del cateterismo intermittente (CIC) o che effettuino minzioni spontanee. In quest’ultimo caso dovranno mostrare un consenso positivo all’eventuale uso di CIC, eventualmente necessario dopo trattamento con tossina botulina A intradetrusoriale.

Caratteristiche urodinamiche: i pazienti devono avere una diagnosi urodinamica di DO refrattaria alla comune terapia standard con anticolinergici, ma devono essere naïve alla terapia con Tossina botulinica intradetrusoriale.
Il wash- out dopo terapia anticolinergica deve essere di almeno 3 settimane.

E.4

Principal exclusion criteria

Exclusion criteria:

- recurring urinary tract infections (UTIs) (= 4 episodes/year);
- spinal cord injuries above T1;
- MS patients: EDSS score = 6;
- patients who won’t or can’t perform intermittent catheterization;
- pregnancy or breast- feeding, if female patients
- post- void residual volume (PRV) > 150 ml, in the case of spontaneous micturition

Criteri di esclusione:
- pazienti affetti da infezioni delle vie urinarie ricorrenti (numero di infezioni urinarie all’anno = 4);
- pazienti con patologie del midollo spinale localizzate al di sopra di T1;
- pazienti con un EDSS =6;
- pazienti che non vogliano o non possano eseguire CIC;
- pazienti donne in gravidanza o allattamento o che intendano iniziare una gravidanza;
- verranno esclusi pazienti che alla minzione spontanea presentino un residuo post- minzionale superiore a 150 ml.

E.5 End points

E.5.1

Primary end point(s)

- Significant reduction in the frequency of urinary incontinence episodes as compared to baseline (according to the 3-day voiding diary) at 2, 4 and 24 weeks after treatment;
- reduction in the frequency of urinary tract infections at 2, 12 and 24 weeks after treatment, with a major (significant reduction) in patients in Group 1 (Incobot/A) as compared to baseline.

- riduzione significativa del numero degli episodi di incontinenza urinaria da urgenza rispetto al basale (valutato mediante il diario minzionale di 3 giorni consecutivi), a 2, 12 e 24 settimane dalla terapia in entrambi i gruppi di trattamento;
- riduzione della frequenza delle infezioni urinarie a 2, 12 e 24 settimane dal trattamento, con una maggiore e significativa riduzione nel Gruppo 1 (Incobot/A) rispetto al basale.

E.5.1.1

Timepoint(s) of evaluation of this end point

2, 12 and 24 weeks

2, 12 e 24 settimane

E.5.2

Secondary end point(s)

- Significant improvements in urodynamic parameters (maximum cystometric capacity, maximum detrusor pressure during first involuntary detrusor contraction) at 12 and 24 weeks as compared to baseline;
- Significant improvement in I-QoL score at 2, 12 and 24 weeks as compared to baseline;
- Assessment of possible adverse events-AE (systemic AEs: fatigue, weakness, dyspnoea, gastrointestinal irritation, dizziness; local AEs: haematuria, dysuria, urinary retention, post-void residual volume > 150 ml, at 2, 12 and 24 weeks after treatment.

- miglioramento significativo dei parametri urodinamici (aumento della massima capacit¿ cistomanometrica, riduzione della pressione detrusoriale nel corso della prima contrazione detrusoriale non inibita) in entrambi i gruppi di trattamento a 12 e 24 settimane dal trattamento rispetto al basale;
- miglioramento significativo dello score del questionario standardizzato I- QoL in entrambi i gruppi di trattamento a 2, 12 e 24 settimane dal trattamento rispetto al basale;
- valutazione di eventuali eventi avversi (sistemici: stanchezza, debolezza generalizzata, difficolt¿ respiratoria, irritazioni gastrointestinali e vertigini; locali: ematuria, infezioni delle vie urinarie, minzione dolorosa, ritenzione urinaria e residuo post minzionale > 150 ml), a 2, 12 e 24 settimane dal trattamento.

E.5.2.1

Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

Yes

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

Yes

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

140

F.4.2

For a multinational trial

F.4.2.1

In the EEA

140

F.4.2.2

In the whole clinical trial

140

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

no plans for treatment at the end of the trial

non sono previsti programmi alcuni al termine dello studio

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-08-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-03-22

P. End of Trial
P.	End of Trial Status	Ongoing

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